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Journal of Alzheimer's Disease : JAD 2024A key aspect of synaptic dysfunction in Alzheimer's disease (AD) is loss of synaptic proteins. Previous publications showed that the presynaptic machinery is more... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A key aspect of synaptic dysfunction in Alzheimer's disease (AD) is loss of synaptic proteins. Previous publications showed that the presynaptic machinery is more strongly affected than postsynaptic proteins. However, it has also been reported that presynaptic protein loss is highly variable and shows region- and protein-specificity.
OBJECTIVE
The objective of this meta-analysis was to provide an update on the available literature and to further characterize patterns of presynaptic protein loss in AD.
METHODS
Systematic literature search was conducted for studies published between 2015-2022 which quantified presynaptic proteins in postmortem tissue from AD patients and healthy controls. Three-level random effects meta-analyses of twenty-two identified studies was performed to characterize overall presynaptic protein loss and changes in specific regions, proteins, protein families, and functional categories.
RESULTS
Meta-analysis confirmed overall loss of presynaptic proteins in AD patients. Subgroup analysis revealed region specificity of protein loss, with largest effects in temporal and frontal cortex. Results concerning different groups of proteins were also highly variable. Strongest and most consistently affected was the family of synaptosome associated proteins, especially SNAP25. Among the most severely affected were proteins regulating dense core vesicle exocytosis and the synaptic vesicle cycle.
CONCLUSIONS
Results confirm previous literature related to presynaptic protein loss in AD patients and provide further in-depth characterization of most affected proteins and presynaptic functions.
Topics: Humans; Alzheimer Disease; Proteins; Presynaptic Terminals
PubMed: 38073390
DOI: 10.3233/JAD-231034 -
Toxins Jan 2022Improvements in Botulinum toxin type-A (BoNT-A) aesthetic treatments have been jeopardized by the simplistic statement: "BoNT-A treats wrinkles". BoNT-A monotherapy...
High Precision Use of Botulinum Toxin Type A (BONT-A) in Aesthetics Based on Muscle Atrophy, Is Muscular Architecture Reprogramming a Possibility? A Systematic Review of Literature on Muscle Atrophy after BoNT-A Injections.
Improvements in Botulinum toxin type-A (BoNT-A) aesthetic treatments have been jeopardized by the simplistic statement: "BoNT-A treats wrinkles". BoNT-A monotherapy relating to wrinkles is, at least, questionable. The BoNT-A mechanism of action is presynaptic cholinergic nerve terminals blockage, causing paralysis and subsequent muscle atrophy. Understanding the real BoNT-A mechanism of action clarifies misconceptions that impact the way scientific productions on the subject are designed, the way aesthetics treatments are proposed, and how limited the results are when the focus is only on wrinkle softening. We designed a systematic review on BoNT-A and muscle atrophy that could enlighten new approaches for aesthetics purposes. A systematic review, targeting articles investigating BoNT-A injection and its correlation to muscle atrophy in animals or humans, filtered 30 publications released before 15 May 2020 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Histologic analysis and histochemistry showed muscle atrophy with fibrosis, necrosis, and an increase in the number of perimysial fat cells in animal and human models; this was also confirmed by imaging studies. A significant muscle balance reduction of 18% to 60% after single or seriated BoNT-A injections were observed in 9 out of 10 animal studies. Genetic alterations related to muscle atrophy were analyzed by five studies and showed how much impact a single BoNT-A injection can cause on a molecular basis. Seriated or single BoNT-A muscle injections can cause real muscle atrophy on a short or long-term basis, in animal models and in humans. Theoretically, muscular architecture reprogramming is a possible new approach in aesthetics.
Topics: Botulinum Toxins, Type A; Humans; Injections, Intramuscular; Muscle, Skeletal; Muscular Atrophy
PubMed: 35202109
DOI: 10.3390/toxins14020081